Opioid receptors are G protein-coupled receptors found in the brain, spinal cord, and digestive tract that have a wide variety of biological function, including controlling pain sensation. There are three recognized “classical” opioid receptor subtypes: mu-opioid receptors (MOR), delta-opioid receptors (DOR), and kappa-opioid receptors (KOR). The natural ligands for opioid receptors include enkephalins, endorphins, endomorphins, and dynorphins, and an abundance of non-peptide or synthetic ligands have been discovered or developed to modulate opioid receptor activity. Opioid drugs, including morphine, are the primary treatment for, e.g., post-operative and chronic pain conditions. Side-effects of opioid administration (e.g., tolerance, drug dependence/addiction, respiration depression, constipation, nausea, pruritis, sedation, and mood swings), however, limit opioids' therapeutic potential.
Despite a considerable amount of research into opioid-based therapeutics, there remains a need for opioid receptor modulators that provide analgesia while minimizing the adverse effects associated with opioid use.